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Summary: High programmed cell death 1 ligand 1 (PD‐L1) protein expression and copy number alterations (CNAs) of the corresponding genomic locus 9p24.1 in Hodgkin‐ and Reed–Sternberg cells (HRSC) have been shown to be associated with favourable response to anti‐PD‐1 checkpoint inhibition in relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In the present study, we investigated baseline 9p24.1 status as well as PD‐L1 and major histocompatibility complex (MHC) class I and II protein expression in 82 biopsies from patients with early stage unfavourable cHL treated with anti‐PD‐1‐based first‐line treatment in the German Hodgkin Study Group (GHSG) NIVAHL trial (ClinicalTrials.gov Identifier: NCT03004833). All evaluated specimens showed 9p24.1 CNA in HRSC to some extent, but with high intratumoral heterogeneity and an overall smaller range of alterations than reported in advanced‐stage or r/r cHL. All but two cases (97%) showed PD‐L1 expression by the tumour cells in variable amounts. While MHC‐I was rarely expressed in >50% of HRSC, MHC‐II expression in >50% of HRSC was found more frequently. No obvious impact of 9p24.1 CNA or PD‐L1 and MHC‐I/II expression on early response to the highly effective anti‐PD‐1‐based NIVAHL first‐line treatment was observed. Further studies evaluating an expanded panel of potential biomarkers are needed to optimally stratify anti‐PD‐1 first‐line cHL treatment. [ABSTRACT FROM AUTHOR]

Summary: We retrospectively investigated histopathological growth patterns in individuals with advanced nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) treated within the randomized HD18 study. In all, 35/60 patients (58%) presented with atypical growth patterns. Patients with atypical growth patterns more often had stage IV disease (P = 0·0354) and splenic involvement (P = 0·0048) than patients with typical growth patterns; a positive positron emission tomography after two cycles of chemotherapy (PET‐2) tended to be more common (P = 0·1078). Five‐year progression‐free survival [hazard ratio (HR) = 0·86; 95% confidence interval (CI) = 0·49–1·47] and overall survival (HR = 0·85; 95% CI = 0·49–1·51) did not differ between the groups after study treatment with PET‐2‐guided escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). Thus, advanced NLPHL is often associated with atypical growth patterns but their prognostic impact is compensated by PET‐2‐guided escalated BEACOPP. [ABSTRACT FROM AUTHOR]

Summary: Data on non‐Hodgkin lymphoma (NHL) after classical Hodgkin lymphoma (cHL) are scarce. We therefore performed a retrospective analysis comprising 11·841 cHL patients who had first‐line treatment within the randomized German Hodgkin Study Group (GHSG) HD7–HD15 studies. After a median follow‐up of 106 months, 175 patients (1·5%) had developed NHL. The median time to NHL was 44 months, the median age at NHL diagnosis was 54 years. The five‐year event‐free survival and overall survival estimates from the diagnosis of NHL were 36·9% and 44·2%, respectively. Thus, NHL after cHL is a rare event primarily affecting older individuals and often resulting in the patient´s death. [ABSTRACT FROM AUTHOR]

Objective: Cancer-related fatigue (CRF) is among the most distressing symptoms reported by cancer survivors as compromising their quality of life. This study investigates the complex interplay between CRF and functional health (FH) in survivors of Hodgkin lymphoma by using longitudinal data to clarify the etiology of CRF. Methods: Data from N = 3596 survivors (HD13-15) from the German Hodgkin Study Group was analyzed using bivariate latent curve models with structured residuals to model how the interplay between CRF and FH unfolds over time across and within individuals. CRF and FH were measured with the EORTC QLQ-C30. Assessed FH domains were physical, cognitive, emotional, social, and role functioning. Age at diagnosis, gender, country, baseline fatigue, and cancer stage were included as covariates. Results: The latent curve models with structured residuals had an adequate model fit (χ² = 416.63-548.28, df = 114, p < .001, root mean square error of approximation = .03, comparative fit index = .98-.99, Tucker-Lewis index = .97-.98). On the between-person level, CRF and all FH domains were strongly negatively correlated (r = -.72 to r = -.84). On the within-person level, earlier CRF (ρF = -.05 to ρF = -.12) and FH deviations (ρFH = -.05 to ρFH = -.13) negatively predicted subsequent deviations of the respective other variable. Time-specific within-person improvements in physical, cognitive, and emotional functioning reduced CRF more than vice versa, whereas the effect of CRF was stronger for social functioning. Role functioning had a balanced relation with CRF. Conclusions: This analysis reveals a complex reciprocal relation between CRF and FH with distinct between- and within-person effects. The results contribute to a better understanding of CRF in survivors of Hodgkin lymphoma and could inform the development of much-needed targeted interventions. [ABSTRACT FROM AUTHOR]

We performed a survey in Hodgkin lymphoma survivors to learn more about their perspectives on treatment risks and benefits. We sent questions to 1149 survivors from the GHSG's HD13-15 trials with (N = 249) or without (N =900) documented progression or relapse. The participation rate was 52% (N =581). After median follow-up of 106 months, 40% of relapse-free and over 60% of relapsed survivors were still worried about late effects and the possibility of relapse. Chemotherapy, largely independent of its intensity, had been a strain on 74% of relapse-free and 90% of relapsed survivors. Most physical, psychological, and socio-economic sequelae were more frequent among relapsed survivors (p <.05) and described as very burdensome. 74% of relapse-free and 61% of relapsed survivors considered primary cure from Hodgkin lymphoma as the most important aspect in the choice of treatment. Accordingly, primary optimal lymphoma control is of utmost importance from the patients' perspective. [ABSTRACT FROM AUTHOR]

Doxorubicin, bleomycin, vinblastine sulfate, and dacarbazine (ABVD) is associated with severe toxicity in older patients, particularly from bleomycin-induced lung toxicity (BLT). Therefore, using bleomycin has been questioned in older Hodgkin lymphoma (HL) patients, especially in early-stage HL. We therefore analyzed feasibility, toxicity, and efficacy of ABVD or AVD in 287 older early-stage favorable HL patients. We included patients ≥60 years of age in the German Hodgkin Study Group HD10 and HD13 trials randomized to either 2 cycles of ABVD (2 x ABVD; n = 137) or AVD (23AVD; n= 82), each followed by involved-field radiotherapy (IF-RT), with patients randomized to 43ABVD1IFRT (n568). Patients' median age was 65 years (range, 60-75) with comparable patient and disease characteristics. Grade III-IV adverse event rates were similar in patients receiving 23AVD and 2 x ABVD (40% and 39%, respectively), but considerably higher in patients receiving 43ABVD (65%). Similarly, BLT was rare in patients receiving 2 x ABVD/AVD, but occurred in 7/69 (10%) of patients randomized to 43ABVD, with 3 lethal events. In conclusion, no effects of bleomycin on toxicity rates were detectable in older patients receiving 2 cycles of chemotherapy. However, we found a high risk of severe toxicity of bleomycin in older HL patients receiving more than 2 cycles of ABVD. These trials are registered at www.clinicaltrials.gov and www.isrctn.com as #NCT00265018 (HD10) and #ISRCTN63474366 (HD13). [ABSTRACT FROM AUTHOR]

Only limited data are available on the role of brentuximab vedotin (SGN-35) in transplant-naive relapsed or refractory patients with Hodgkin lymphoma (HL). We thus retrospectively analyzed 14 patients with primary refractory or relapsed HL who were treated with brentuximab vedotin as single agent in a named patient program, who had not received prior high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) due to refractory disease ( n = 9), comorbidity ( n = 4) and unknown reasons ( n = 1). Brentuximab vedotin resulted in an overall response rate of 71% (10/14) with five complete responses (CRs). Five of those patients with refractory disease and four patients with relevant comorbidity responded. Consolidating ASCT ( n = 4) or allogeneic SCT ( n = 1) was performed in five patients. Median progression-free survival (PFS) was 9 months and the median overall survival (OS) was not reached. These data indicate the therapeutic efficacy of brentuximab vedotin in chemotherapy-refractory transplant-naive patients with HL. [ABSTRACT FROM AUTHOR]

The CD30-targeting Ab-drug conjugate brentuximab vedotin (SGN-35) was re-cently approved for the treatment of re-lapsed Hodgkin lymphoma and anaplas-tic large-cell lymphoma by the Food and Drug Administration. In the present study, we report the experience of the German Hodgkin Study Group with brentuximab vedotin as single agent In 45 patients with refractory or relapsed CD30+ Hodgkin lymphoma who were treated either in a named patient program (n = 34) or in the context of a safety study associated with the registration program of this drug. In these very heavily pretreated patients, an objective response rate of 60%, Including 22% complete remissions, could be docu-mented. The median duration of response was 8 months. This retrospective analy-sis supports the previously reported ex-cellent therapeutic efficacy of brentux-imab vedotin in heavily pretreated CD30+ malignancies. [ABSTRACT FROM AUTHOR]